PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-21 (21)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
1.  Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs 
BMC Medicine  2005;3:21.
Background
Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.
Methods
A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24–28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.
Results
The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.
Conclusion
Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.
doi:10.1186/1741-7015-3-21
PMCID: PMC1327673  PMID: 16375765
2.  Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management 
BMC Medicine  2005;3:20.
Background
Cyclic Vomiting Syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting and other symptoms, separated by intervals of comparative wellness. This report describes the clinical features, co-morbidities and problems encountered in management of 41 adult patients who met the diagnostic criteria for CVS.
Methods
This is a retrospective study of adults with CVS seen between 1994 and 2003. Follow-up data were obtained by mailed questionnaires.
Results
Age of onset ranged from 2 to 49 years. The duration of CVS at the time of consultation ranged from less than 1 year to 49 years. CVS episodes were stereotypic in respect of their hours of onset, symptomatology and length. Ninety-three percent of patients had recognizable prodromes. Half of the patients experienced a constellation of symptoms consisting of CVS episodes, migraine diathesis, inter-episodic dyspeptic nausea and a history of panic attacks. Deterioration in the course of CVS is indicated by coalescence of episodes in time. The prognosis of CVS is favorable in the majority of patients.
Conclusion
CVS is a disabling disorder affecting adults as well as children. Because its occurrence in adults is little known, patients experience delayed or mis-diagnosis and ineffectual, sometimes inappropriately invasive management.
doi:10.1186/1741-7015-3-20
PMCID: PMC1326207  PMID: 16368014
3.  Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study 
BMC Medicine  2005;3:19.
Background
The lack of standardized criteria for defining chronic fatigue syndrome (CFS) has constrained research. The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria.
Methods
This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n = 28). Participants were admitted to a hospital for two days and underwent medical history and physical examination, the Diagnostic Interview Schedule, and laboratory testing to identify medical and psychiatric conditions exclusionary for CFS. Illness classification at the time of the clinical study utilized two algorithms: (1) the same criteria as in the surveillance study; (2) a standardized clinically empirical algorithm based on quantitative assessment of the major domains of CFS (impairment, fatigue, and accompanying symptoms).
Results
One hundred and sixty-four participants had no exclusionary conditions at the time of this study. Clinically empirical classification identified 43 subjects as CFS, 57 as ISF, and 64 as not ill. There was minimal association between the empirical classification and classification by the surveillance criteria. Subjects empirically classified as CFS had significantly worse impairment (evaluated by the SF-36), more severe fatigue (documented by the multidimensional fatigue inventory), more frequent and severe accompanying symptoms than those with ISF, who in turn had significantly worse scores than the not ill; this was not true for classification by the surveillance algorithm.
Conclusion
The empirical definition includes all aspects of CFS specified in the 1994 case definition and identifies persons with CFS in a precise manner that can be readily reproduced by both investigators and clinicians.
doi:10.1186/1741-7015-3-19
PMCID: PMC1334212  PMID: 16356178
4.  The course of mental health after miscarriage and induced abortion: a longitudinal, five-year follow-up study 
BMC Medicine  2005;3:18.
Background
Miscarriage and induced abortion are life events that can potentially cause mental distress. The objective of this study was to determine whether there are differences in the patterns of normalization of mental health scores after these two pregnancy termination events.
Methods
Forty women who experienced miscarriages and 80 women who underwent abortions at the main hospital of Buskerud County in Norway were interviewed. All subjects completed the following questionnaires 10 days (T1), six months (T2), two years (T3) and five years (T4) after the pregnancy termination: Impact of Event Scale (IES), Quality of Life, Hospital Anxiety and Depression Scale (HADS), and another addressing their feelings about the pregnancy termination. Differential changes in mean scores were determined by analysis of covariance (ANCOVA) and inter-group differences were assessed by ordinary least squares methods.
Results
Women who had experienced a miscarriage had more mental distress at 10 days and six months after the pregnancy termination than women who had undergone an abortion. However, women who had had a miscarriage exhibited significantly quicker improvement on IES scores for avoidance, grief, loss, guilt and anger throughout the observation period. Women who experienced induced abortion had significantly greater IES scores for avoidance and for the feelings of guilt, shame and relief than the miscarriage group at two and five years after the pregnancy termination (IES avoidance means: 3.2 vs 9.3 at T3, respectively, p < 0.001; 1.5 vs 8.3 at T4, respectively, p < 0.001). Compared with the general population, women who had undergone induced abortion had significantly higher HADS anxiety scores at all four interviews (p < 0.01 to p < 0.001), while women who had had a miscarriage had significantly higher anxiety scores only at T1 (p < 0.01).
Conclusion
The course of psychological responses to miscarriage and abortion differed during the five-year period after the event. Women who had undergone an abortion exhibited higher scores during the follow-up period for some outcomes. The difference in the courses of responses may partly result from the different characteristics of the two pregnancy termination events.
doi:10.1186/1741-7015-3-18
PMCID: PMC1343574  PMID: 16343341
5.  Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population 
BMC Medicine  2005;3:17.
Background
Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients.
Methods
We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year.
Results
Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac.
Conclusion
This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.
doi:10.1186/1741-7015-3-17
PMCID: PMC1310534  PMID: 16316472
6.  Self-prescribing among young Norwegian doctors: a nine-year follow-up study of a nationwide sample 
BMC Medicine  2005;3:16.
Background
Self-prescribing among doctors is common, but no longitudinal studies have documented this issue. We studied the self-prescribing behaviour among young Norwegian physicians and the predictors of self-prescribing.
Methods
We conducted a nationwide, prospective and longitudinal study following young Norwegian physicians from internship through the subsequent nine years using three postal questionnaires. Chi-square tests and logistic regression models were applied.
Results
About 54% of the physicians in their fourth and ninth postgraduate years had self-prescribed medication at least once during the previous year. Among those who had used prescription medication during the previous year, about 90% had self-prescribed. Self-prescribing behaviour did not differ significantly between men and women, or according to the type of work at any time. The most frequently self-prescribed medications were antibiotics (71%–81%), contraceptives (24%–25%), analgesics (18%–21%), and hypnotics (9%–12%). Those who had needed treatment for mental problems had self-prescribed hypnotics and sedatives to a greater extent than the others. Being male, having self-prescribed during internship, somatic complaints, mental distress, subjective health complaints, and not having sought help from a general practitioner, were significant adjusted predictors of self-prescribing in the ninth postgraduate year.
Conclusion
The level of self-prescribing among young Norwegian physicians is relatively high, and this behaviour is established early in their professional lives. Although self-prescribing is acceptable in some situations, physicians should seek professional help for illness. Efforts to inculcate more rational help-seeking behaviour should probably start in medical schools.
doi:10.1186/1741-7015-3-16
PMCID: PMC1276798  PMID: 16242034
7.  Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials 
BMC Medicine  2005;3:15.
Background
Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.
Methods
We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.
Results
Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.
Conclusion
It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.
doi:10.1186/1741-7015-3-15
PMCID: PMC1274318  PMID: 16229742
8.  Suicide attempts in clinical trials with paroxetine randomised against placebo 
BMC Medicine  2005;3:14.
Background
Inclusion of unpublished data on the effects of antidepressants on children has suggested unfavourable risk-benefit profiles for some of the drugs. Recent meta-analyses of studies on adults have indicated similar effects. We obtained unpublished data for paroxetine that have so far not been included in these analyses.
Methods
The documentation for drug registration contained 16 studies in which paroxetine had been randomised against placebo. We registered the number of suicides, suicide attempts and ideation. We corrected for duration of medication and placebo treatment and used a standard Bayesian statistical approach with varying priors.
Results
There were 7 suicide attempts in patients on the drug and 1 in a patient on placebo. We found that the probability of increased intensity of suicide attempts per year in adults taking paroxetine was 0.90 with a "pessimistic" prior, and somewhat less with two more neutral priors.
Conclusion
Our findings support the results of recent meta-analyses. Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may also be present in adults.
doi:10.1186/1741-7015-3-14
PMCID: PMC1198229  PMID: 16115311
9.  Changes in standard of candidates taking the MRCP(UK) Part 1 examination, 1985 to 2002: Analysis of marker questions 
BMC Medicine  2005;3:13.
Background
The maintenance of standards is a problem for postgraduate medical examinations, particularly if they use norm-referencing as the sole method of standard setting. In each of its diets, the MRCP(UK) Part 1 Examination includes a number of marker questions, which are unchanged from their use in a previous diet. This paper describes two complementary studies of marker questions for 52 diets of the MRCP(UK) Part 1 Examination over the years 1985 to 2001 to assess whether standards have changed.
Methods
Study 1, which used routinely collected information on the performance of 4405 marker items, used a statistical method to assess changes in performance across diets. Study 2 compared performances of individual candidates on 28 individual marker items that were shared by the 1996/2 and 2001/3 diets.
Results
Study 1 found evidence that candidate performance on the MRCP(UK) Part 1 Examination showed a gradual improvement over the period 1985 to 1997, which was followed by a sharp decline in performance until 2001. The 'dog-leg' in performance at 1997/3 was not an artefact of changed Examination Regulations, mix of UK and overseas candidates, or time from qualification until taking the Examination. Study 2 confirmed that performance in 2001/3 was significantly worse than in 1996/3, that the poorer performance was found in graduates of UK medical schools, and that candidates passing the Examination in 2001/3 performed less well than those passing in 1996/2.
Conclusion
There has been a decline in the performance of graduates from UK medical schools taking the MRCP(UK) Part 1 examination. The reasons for this are not clear, but the finding has implications for medical education, and further studies are needed of performance in other postgraduate and undergraduate examinations. The use of norm-referencing as the sole method for setting the pass mark over this period meant that candidates passing the MRCP(UK) examination also had a lower standard. The MRCP(UK) Part 1 and Part 2 examinations now have their standard set by criterion-referencing.
doi:10.1186/1741-7015-3-13
PMCID: PMC1185541  PMID: 16026607
10.  Public beliefs about treatment and outcome of mental disorders: a comparison of Australia and Japan 
BMC Medicine  2005;3:12.
Background
Surveys of the public in a number of countries have shown poor recognition of mental disorders and beliefs about treatment that often diverge from those of health professionals. This lack of mental health literacy can limit the optimal use of treatment services. Australia and Japan are countries with very different mental health care systems, with Japan emphasising hospital care and Australia more oriented to community care. Japan is also more collectivist and Australia more individualist in values. These differences might influence recognition of disorders and beliefs about treatment in the two countries.
Methods
Surveys of the public were carried out in each country using as similar a methodology as feasible. In both countries, household interviews were carried out concerning beliefs in relation to one of four case vignettes, describing either depression, depression with suicidal thoughts, early schizophrenia or chronic schizophrenia. In Australia, the survey involved a national sample of 3998 adults aged 18 years or over. In Japan, the survey involved 2000 adults aged between 20 and 69 from 25 regional sites spread across the country.
Results
The Japanese public were found to be more reluctant to use psychiatric labels, particularly for the depression cases. The Japanese were also more reluctant to discuss mental disorders with others outside the family. They had a strong belief in counsellors, but not in GPs. They generally believe in the benefits of treatment, but are not optimistic about full recovery. By contrast, Australians used psychiatric labels more often, particularly "depression". They were also more positive about the benefits of seeking professional help, but had a strong preference for lifestyle interventions and tended to be negative about some psychiatric medications. Australians were positive about both counsellors and GPs. Psychiatric hospitalization and ECT were seen negatively in both countries.
Conclusion
There are some major differences between Australia and Japan in recognition of disorders and beliefs about treatment. Some of these may relate to the different health care systems, but the increasing openness about mental health in Australia is also likely to be an explanatory factor.
doi:10.1186/1741-7015-3-12
PMCID: PMC1177951  PMID: 16004615
11.  The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system 
BMC Medicine  2005;3:11.
Background
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations.
Methods
Baboons were randomized into a breastfed (B) and four formula-fed groups: term, no DHA/ARA (T-); term, DHA/ARA supplemented (T+); preterm, no DHA/ARA (P-); preterm and DHA/ARA supplemented (P+). At four weeks adjusted age, brains were dissected and total fatty acids analyzed by gas chromatography and mass spectrometry.
Results
DHA and ARA are rich in many more structures than previously reported. They are most concentrated in structures local to the brain stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus and midbrain, and comparatively lower in white matter. Dietary supplementation increased DHA in all structures but had little influence on ARA concentrations. Supplementation restored DHA concentrations to levels of breastfed neonates in all regions except the cerebral cortex and cerebellum. Prematurity per se did not exert a strong influence on DHA or ARA concentrations.
Conclusion
1) DHA and ARA are found in high concentration throughout the primate CNS, particularly in gray matter such as basal ganglia; 2) DHA concentrations drop across most CNS structures in neonates consuming formulas with no DHA, but ARA levels are relatively immune to ARA in the diet; 3) supplementation of infant formula is effective at restoring DHA concentration in structures other than the cerebral cortex. These results will be useful as a guide to future investigations of CNS function in the absence of dietary DHA and ARA.
doi:10.1186/1741-7015-3-11
PMCID: PMC1184078  PMID: 15975147
12.  Age-related human small intestine methylation: evidence for stem cell niches 
BMC Medicine  2005;3:10.
Background
The small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells. Very little is known about human small intestines because mouse fate mapping strategies are impractical in humans. However, it is theoretically possible that stem cell histories are inherently written within their genomes. Genomes appear to record histories (as exemplified by use of molecular clocks), and therefore it may be possible to reconstruct somatic cell dynamics from somatic cell errors. Recent human colon studies suggest that random somatic epigenetic errors record stem cell histories (ancestry and total numbers of divisions). Potentially age-related methylation also occurs in human small intestines, which would allow characterization of their stem cells and comparisons with the colon.
Methods
Methylation patterns in individual crypts from 13 small intestines (17 to 78 years old) were measured by bisulfite sequencing. The methylation patterns were analyzed by a quantitative model to distinguish between immortal or niche stem cell lineages.
Results
Age-related methylation was observed in the human small intestines. Crypt methylation patterns were more consistent with stem cell niches than immortal stem cell lineages. Human large and small intestine crypt niches appeared to have similar stem cell dynamics, but relatively less methylation accumulated with age in the small intestines. There were no apparent stem cell differences between the duodenum and ileum, and stem cell survival did not appear to decline with aging.
Conclusion
Crypt niches containing multiple stem cells appear to maintain human small intestines. Crypt niches appear similar in the colon and small intestine, and the small intestinal stem cell mitotic rate is the same as or perhaps slower than that of the colon. Although further studies are needed, age-related methylation appears to record somatic cell histories, and a somatic epigenetic molecular clock strategy may potentially be applied to other human tissues to reconstruct otherwise occult stem cell histories.
doi:10.1186/1741-7015-3-10
PMCID: PMC1168897  PMID: 15975143
13.  The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616] 
BMC Medicine  2005;3:9.
Background
Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial.
Methods
Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge.
Results
There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01).
Conclusion
Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients.
doi:10.1186/1741-7015-3-9
PMCID: PMC1177952  PMID: 15932638
14.  Psychological illness is commonly associated with functional gastrointestinal disorders and is important to consider during patient consultation: a population-based study 
BMC Medicine  2005;3:8.
Background
Some individuals with functional gastrointestinal disorders (FGID) suffer long-lasting symptoms without ever consulting their doctors. Our aim was to study co-morbidity and lifestyle differences among consulters and non-consulters with persistent FGID and controls in a defined adult population.
Methods
A random sample of the general adult Swedish population was obtained by a postal questionnaire. The Abdominal Symptom Questionnaire (ASQ) was used to measure GI symptomatology and grade of GI symptom severity and the Complaint Score Questionnaire (CSQ) was used to measure general symptoms. Subjects were then grouped for study by their symptomatic profiles. Subjects with long-standing FGID (n = 141) and subjects strictly free from gastrointestinal (GI) symptoms (n = 97) were invited to attend their local health centers for further assessment.
Results
Subjects with FGID have a higher risk of psychological illness [OR 8.4, CI95(4.0–17.5)] than somatic illness [OR 2.8, CI95(1.3–5.7)] or ache and fatigue symptoms [OR 4.3, CI95(2.1–8.7)]. Subjects with psychological illness have a higher risk of severe GI symptoms than controls; moreover they have a greater chance of being consulters. Patients with FGID have more severe GI symptoms than non-patients.
Conclusion
There is a strong relation between extra-intestinal, mental and somatic complaints and FGID in both patients and non-patients. Psychological illness increases the chance of concomitantly having more severe GI symptoms, which also enhance consultation behaviour.
doi:10.1186/1741-7015-3-8
PMCID: PMC1156899  PMID: 15892883
15.  EMBASE search strategies for identifying methodologically sound diagnostic studies for use by clinicians and researchers 
BMC Medicine  2005;3:7.
Background
Accurate diagnosis by clinicians is the cornerstone of decision making for recommending clinical interventions. The current best evidence from research concerning diagnostic tests changes unpredictably as science advances. Both clinicians and researchers need dependable access to published evidence concerning diagnostic accuracy. Bibliographic databases such as EMBASE provide the most widely available entrée to this literature. The objective of this study was to develop search strategies that optimize the retrieval of methodologically sound diagnostic studies from EMBASE for use by clinicians.
Methods
An analytic survey was conducted, comparing hand searches of 55 journals with retrievals from EMBASE for 4,843 candidate search terms and 6,574 combinations. All articles were rated using purpose and quality indicators, and clinically relevant diagnostic accuracy articles were categorized as 'pass' or 'fail' according to explicit criteria for scientific merit. Candidate search strategies were run in EMBASE, the retrievals being compared with the hand search data. The proposed search strategies were treated as "diagnostic tests" for sound studies and the manual review of the literature was treated as the "gold standard." The sensitivity, specificity, precision and accuracy of the search strategies were calculated.
Results
Of the 433 articles about diagnostic tests, 97 (22.4%) met basic criteria for scientific merit. Combinations of search terms reached peak sensitivities of 100% with specificity at 70.4%. Compared with best single terms, best multiple terms increased sensitivity for sound studies by 8.2% (absolute increase), but decreased specificity (absolute decrease 6%) when sensitivity was maximized. When terms were combined to maximize specificity, the single term "specificity.tw." (specificity of 98.2%) outperformed combinations of terms.
Conclusion
Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and specificity for retrieving sound diagnostic studies from EMBASE. These search filters will enhance the searching efforts of clinicians.
doi:10.1186/1741-7015-3-7
PMCID: PMC1079845  PMID: 15796772
16.  The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial [ISRCTN48489393] 
BMC Medicine  2005;3:6.
Background
There have been concerns that low blood cholesterol concentrations may cause non-vascular mortality and morbidity. Randomisation of large numbers of people to receive a large, and prolonged, reduction in cholesterol concentrations provides an opportunity to address such concerns reliably.
Methods
20,536 UK adults (aged 40–80 years) with vascular disease or diabetes were randomly allocated to receive 40 mg simvastatin daily or matching placebo. Prespecified safety analyses were of cause-specific mortality, and of total and site-specific cancer incidence. Comparisons between all simvastatin-allocated versus all placebo-allocated participants (ie, "intention-to-treat") involved an average difference in blood total cholesterol concentration of 1.2 mmol/L (46 mg/dL) during the scheduled 5-year treatment period.
Results
There was a highly significant 17% (95% CI 9–25) proportional reduction in vascular deaths, along with a non-significant reduction in all non-vascular deaths, which translated into a significant reduction in all-cause mortality (p = 0.0003). The proportional reduction in the vascular mortality rate was about one-sixth in each subcategory of participant studied, including: men and women; under and over 70 years at entry; and total cholesterol below 5.0 mmol/L or LDL cholesterol below 3.0 mmol/L. No significant excess of non-vascular mortality was observed in any subcategory of participant (including the elderly and those with pretreatment total cholesterol below 5.0 mmol/L), and there was no significant excess in any particular cause of non-vascular mortality.
Cancer incidence rates were similar in the two groups, both overall and in particular subcategories of participant, as well as at particular primary sites. There was no suggestion that any adverse trends in non-vascular mortality or morbidity were beginning to emerge with more prolonged treatment.
Conclusion
These findings, which are based on large numbers of deaths and non-fatal cancers, provide considerable reassurance that lowering total cholesterol concentrations by more than 1 mmol/L for an average of 5 years does not produce adverse effects on non-vascular mortality or cancer incidence. Moreover, among the many different types of high-risk individual studied, simvastatin 40 mg daily consistently produced substantial reductions in vascular (and, hence, all-cause) mortality, as well as in the rates of non-fatal heart attacks, strokes and revascularisation procedures.
doi:10.1186/1741-7015-3-6
PMCID: PMC1079844  PMID: 15771782
17.  Khat use as risk factor for psychotic disorders: A cross-sectional and case-control study in Somalia 
BMC Medicine  2005;3:5.
Background
Little is known about the prevalence of khat-induced psychotic disorders in East African countries, where the chewing of khat leaves is common. Its main psycho-active component cathinone produces effects similar to those of amphetamine. We aimed to explore the prevalence of psychotic disorders among the general population and the association between khat use and psychotic symptoms.
Methods
In an epidemiological household assessment in the city of Hargeisa, North-West Somalia, trained local interviewers screened 4,854 randomly selected persons from among the general population for disability due to severe mental problems. The identified cases were interviewed based on a structured interview and compared to healthy matched controls. Psychotic symptoms were assessed using the items of the WHO Composite International Diagnostic Interview and quantified with the Positive and Negative Symptoms Scale. Statistical testing included Student's t-test and ANOVA.
Results
Local interviewers found that rates of severe disability due to mental disorders were 8.4% among males (above the age of 12) and differed according to war experiences (no war experience: 3.2%; civilian war survivors: 8.0%; ex-combatants: 15.9%). The clinical interview verified that in 83% of positive screening cases psychotic symptoms were the most prominent manifestations of psychiatric illness. On average, cases with psychotic symptoms had started to use khat earlier in life than matched controls and had been using khat 8.6 years before positive symptoms emerged. In most cases with psychotic symptoms, a pattern of binge use (> two 'bundles' per day) preceded the onset of psychotic symptoms, in contrast to controls of the same age. We found significant correlations between variables of khat consumption and clinical scales (0.35 to 0.50; p < 0.05), and between the age of onset of khat chewing and symptom onset (0.70; p <0.001).
Conclusion
Evidence indicates a relationship between the consumption of khat and the onset of psychotic symptoms among the male population, whereby not the khat intake per se but rather early onset and excessive khat chewing seemed to be related to psychotic symptoms. The khat problem must be addressed by means other than prohibition, given the widespread use and its role in Somali culture.
doi:10.1186/1741-7015-3-5
PMCID: PMC554104  PMID: 15707502
18.  Sudden Infant Death Syndrome and prenatal maternal smoking: rising attributed risk in the Back to Sleep era 
BMC Medicine  2005;3:4.
Background
Parental smoking and prone sleep positioning are recognized causal features of Sudden Infant Death. This study quantifies the relationship between prenatal smoking and infant death over the time period of the Back to Sleep campaign in the United States, which encouraged parents to use a supine sleeping position for infants.
Methods
This retrospective cohort study utilized the Colorado Birth Registry. All singleton, normal birth weight infants born from 1989 to 1998 were identified and linked to the Colorado Infant Death registry. Multivariable logistic regression was used to analyze the relationship between outcomes of interest and prenatal maternal cigarette use. Potential confounders analyzed included infant gender, gestational age, and birth year as well as maternal marital status, ethnicity, pregnancy interval, age, education, and alcohol use.
Results
We analyzed 488,918 birth records after excluding 5835 records with missing smoking status. Smokers were more likely to be single, non-Hispanic, less educated, and to report alcohol use while pregnant (p < 0.001). The study included 598 SIDS cases of which 172 occurred in smoke-exposed infants. Smoke exposed infants were 1.9 times (95% CI 1.6 to 2.3) more likely to die of SIDS. The attributed risk associating smoking and SIDS increased during the study period from approximately 50% to 80%. During the entire study period 59% (101/172) of SIDS deaths in smoke-exposed infants were attributed to maternal smoking.
Conclusions
Due to a decreased overall rate of SIDS likely due to changing infant sleep position, the attributed risk associating maternal smoking and SIDS has increased following the Back to Sleep campaign. Mothers should be informed of the 2-fold increased rate of SIDS associated with maternal cigarette consumption.
doi:10.1186/1741-7015-3-4
PMCID: PMC545061  PMID: 15644131
Sudden Infant Death Syndrome; SIDS; smoking; infant death; attributed risk
19.  Blood pressure demographics: nature or nurture ... ... genes or environment? 
BMC Medicine  2005;3:3.
Hypertension is a growing worldwide problem associated with an increased risk of cardiovascular morbidity and mortality. However, the rates of prevalence of hypertension are higher in some populations than others. Although ethnic and genetic factors have been implied in the past to explain this, the environmental influence and psychosocial factors may play a more important role than is widely accepted. Examining the non-genetic influences in future hypertension research may be necessary in order to clearly define the local blood pressure demographics and the global hypertensive disease burden.
doi:10.1186/1741-7015-3-3
PMCID: PMC544878  PMID: 15638936
Hypertension; prevalence; genetic; environment; psychosocial factors
20.  An international comparative study of blood pressure in populations of European vs. African descent 
BMC Medicine  2005;3:2.
Background
The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue.
Methods
Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants).
Results
The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks.
Conclusions
These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.
doi:10.1186/1741-7015-3-2
PMCID: PMC545060  PMID: 15629061
21.  Recurrent cardiac events in patients with idiopathic ventricular fibrillation, excluding patients with the Brugada syndrome 
BMC Medicine  2005;3:1.
Background
The recurrence of cardiac events in patients with idiopathic ventricular fibrillation (VF) excluding patients with the Brugada syndrome is unclear since this entity remains present in previous studies.
Methods
Since 1992, 18 patients (72% male) with idiopathic VF out of 455 ICD implants were treated with an implantable cardioverter defibrillator (ICD). The mean age at first ICD implantation was 42 ± 14 years. Brugada syndrome, as well as other primary electrical diseases (e.g. long QT), were systematically excluded in all patients by the absence of the typical electrocardiogram (ST elevation in the right precordial leads) at rest and/or after pharmacological tests (ajmaline, flecainide, or procainamide). Recurrence of cardiac events was prospectively assessed.
Results
During a mean follow-up period of 41 ± 27 months, VF recurrence with appropriate shock occurred in 7 patients (39%) covering a total of 27 shocks. The median time to first appropriate shock was 12 ± 9 months. There were no deaths. In the electrophysiological study, 39% of patients were inducible, but inducibility failed to predict subsequent arrhythmic events. Forty-four percent of patients suffered 21 inappropriate shocks, which were caused by sinus tachycardia, atrial arrhythmias or lead malfunction.
Conclusion
Idiopathic ventricular fibrillation patients have a high recurrence rate of potentially fatal ventricular arrhythmias, excluding patients with the Brugada syndrome or other known causes. ICD prevents sudden cardiac death but inappropriate shocks remained a major issue in this young and active population.
doi:10.1186/1741-7015-3-1
PMCID: PMC545059  PMID: 15627402

Results 1-21 (21)